Expression of specific genes and production of the cognate encoded proteins within cells and tissues is dependent in part upon the metabolic state of the cell or tissue. Certain genes are expressed only at specific developmental stages, such as the fetal stage. A protein may be produced in one tissue during fetal development, and in another tissue during the adult stage. Other proteins may be produced during fetal development but not in normal adult tissue.
Genes may be expressed in abnormal amounts or abnormal locations in some pathological states, particularly in cancers. Gene expression and protein production are therefore indicators of the metabolic state of cells and tissues. For example, production of a particular protein in a certain tissue may be indicative of a cancerous or pre-cancerous state. Cancer-specific proteins may also be released by cells into bodily fluids, where they can be detected by conventional diagnostic methods.
Cancer-specific gene expression also provides targets for therapeutic intervention. By reducing or blocking such gene expression or by interfering in the biological activity of the encoded protein, tumor development may be slowed or reversed. Tumor-specific proteins also provide targets for the delivery of therapeutic agents, providing for more specific treatment with reduced side effects.
Within one aspect of the invention there is provided an isolated polypeptide comprising at least nine contiguous amino acid residues of SEQ ID NO:2 or SEQ ID NO:5. Within one embodiment, the isolated polypeptide consists of from 15 to 1500 amino acid residues. Within another embodiment, the at least nine contiguous amino acid residues of SEQ ID NO:2 or SEQ ID NO:5 are operably linked via a peptide bond or polypeptide linker to a second polypeptide selected from the group consisting of maltose binding protein, an immunoglobulin constant region, a polyhistidine tag, and a peptide as shown in SEQ ID NO:3. Within another embodiment, the isolated polypeptide comprises at least 30 contiguous residues of SEQ ID NO:2 or SEQ ID NO:5. Exemplary polypeptides of the invention include, without limitation, those comprising residues 2-8, 15-22, 38-45, 94-99, 110-115, 196-202, 215-220, 235-241, 2-22, 110-133, 120-133, 121-132, 192-203, 214-226, or 214-242 SEQ ID NO:2.
Within a second aspect of the invention there is provided an expression vector comprising the following operably linked elements: a transcription promoter, a DNA segment encoding a protein comprising residues 1-248 of SEQ ID NO:2 or SEQ ID NO:5, and a transcription terminator. Within one embodiment, the DNA segment comprises nucleotides 174-917 of SEQ ID NO:1. Within another embodiment, the expression vector further comprises a secretory signal sequence operably linked to the DNA segment.
Within a third aspect of the invention there is provided a cultured cell into which has been introduced an expression vector as disclosed above, wherein the cell expresses the DNA segment. Within one embodiment, the expression vector comprises a secretory signal sequence operably linked to the DNA segment, and the protein is secreted by the cell. The cultured cell of the invention can be used, inter alia, within a method of making a protein, wherein the cell is cultured under conditions whereby the DNA segment is expressed and the protein is produced, and the protein is recovered. Within one embodiment, the expression vector comprises a secretory signal sequence operably linked to the DNA segment, the protein is secreted by the cell, and the protein is recovered from a medium in which the cell is cultured.
Within a fourth aspect of the invention there is provided a protein produced by the method disclosed above.
Within a fifth aspect of the invention there is provided an antibody that specifically binds to a protein as disclosed above. Within one embodiment of the invention the antibody is labeled to produce a detectable signal.
Within a sixth aspect of the invention there is provided a method of detecting, in a test sample, a polypeptide selected from the group consisting of (a) a polypeptide as shown in SEQ ID NO:2, (b) a polypeptide as shown in SEQ ID NO:5, and (c) proteolytic fragments of (a) or (b). The method comprises combining the test sample with an antibody as disclosed above under conditions whereby the antibody binds to the polypeptide, and detecting the presence of antibody bound to the polypeptide.
Within a seventh aspect of the invention there are provided isolated polynucleotides encoding the polypeptides disclosed above. Within one aspect of the invention the isolated polynucleotide comprises nucleotides 1-744 of SEQ ID NO:4 or SEQ ID NO:6. Within another aspect of the invention the isolated polynucleotide comprises nucleotides 174-917 of SEQ ID NO:1.